The pan-cancer landscape of crosstalk between leukocyte transendothelial migration-related genes and tumor microenvironment relevant to prognosis and immunotherapy response.
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引用次数: 0
Abstract
Background: Leukocyte transendothelial migration-related genes (LTEMGs) play a crucial role in the immune response and have been extensively studied in various pathological conditions, including inflammation, infection, and cancer. In recent years, increasing attention has been given to understanding the biological mechanisms of LTEMGs in the context of tumor progression and metastasis. The potential function of LTEMGs in cancer progression remains unclear. The aim of this study is to systematically delineate the relationship between LTEMGs and tumor prognosis and immune microenvironment at the pan-cancer level, providing new biomarkers for personalized immunotherapy.
Methods: The gene alteration, messenger RNA (mRNA) expression, and prognostic value of LTEMGs in pan-cancer were evaluated using Bulk and single-cell RNA (scRNA) sequence data. The LTEMGs score was calculated by R package "GSVA". The association of LTEMGs score with tumor microenvironment and immunotherapy response were deeply explored.
Results: We assessed the mRNA expression of 114 LTEMGs across various cancers, finding significant upregulation in acute myeloid leukemia (LAML) and pancreatic adenocarcinoma (PAAD). Prognostic analysis indicated most LTEMGs were risk factors in low-grade glioma (LGG), PAAD, uveal melanoma (UVM), and LAML. The LTEMGs score, highest in kidney renal clear cell carcinoma (KIRC) and lowest in UVM, was higher in tumor tissues compared to normal tissues in several cancers. The score was a risk factor for overall survival (OS) in LGG, UVM, and others, but protective in KIRC and some others. LTEMGs score correlated positively with Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling, apoptosis, and immune responses. It also correlated with immune and stromal scores, and immune-related pathways. Higher LTEMGs score was linked to greater immune cell infiltration and poorer immunotherapy outcomes. Single-cell analysis revealed higher LTEMGs score in endothelial and monocyte cells, consistent with reduced immunotherapy responsiveness.
Conclusions: Our results reveal that LTEMGs are closely associated with tumor microenvironment. Patients with high LTEMGs score might be resistant to immunotherapy.
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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